ATL1

Summary

ATL1 (atlastin GTPase 1, HGNC:11231) is a protein-coding gene on chromosome 14q22.1, encoding Atlastin-1 (Q8WXF7). Atlastin-1 (ATL1) is a membrane-anchored GTPase that mediates the GTP-dependent fusion of endoplasmic reticulum (ER) membranes, maintaining the continuous ER network.

The protein encoded by this gene is a GTPase and a Golgi body transmembrane protein. The encoded protein can form a homotetramer and has been shown to interact with spastin and with mitogen-activated protein kinase kinase kinase kinase 4. This protein may be involved in axonal maintenance as evidenced by the fact that defects in this gene are a cause of spastic paraplegia type 3. Three transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 51062 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neuropathy, hereditary sensory, type 1D (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 698 total — 40 pathogenic, 41 likely-pathogenic
• Phenotypes (HPO): 73
• MANE Select transcript: NM_015915

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11231
Approved symbol	ATL1
Name	atlastin GTPase 1
Location	14q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FSP1, AD-FSP
Ensembl gene	ENSG00000198513
Ensembl biotype	protein_coding
OMIM	606439
Entrez	51062

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 17 protein_coding, 10 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000358385, ENST00000441560, ENST00000553509, ENST00000553746, ENST00000554886, ENST00000555266, ENST00000555960, ENST00000556067, ENST00000556478, ENST00000557735, ENST00000674288, ENST00000674478, ENST00000674503, ENST00000682037, ENST00000682219, ENST00000682226, ENST00000682487, ENST00000683037, ENST00000683315, ENST00000683330, ENST00000683703, ENST00000683837, ENST00000684737, ENST00000713928, ENST00000713929, ENST00000713930, ENST00000713931, ENST00000868185, ENST00000868186, ENST00000932063, ENST00000945455

RefSeq mRNA: 3 — MANE Select: NM_015915 NM_001127713, NM_015915, NM_181598

CCDS: CCDS32077, CCDS9700

Canonical transcript exons

ENST00000358385 — 14 exons

Exon	Start	End
ENSE00001001525	50614373	50614511
ENSE00001001527	50595576	50595632
ENSE00001001529	50620599	50620726
ENSE00001001530	50613259	50613351
ENSE00001001532	50593846	50593896
ENSE00001001534	50628031	50628462
ENSE00001672165	50560145	50560299
ENSE00001754719	50629995	50630009
ENSE00001881929	50632229	50633045
ENSE00003518779	50590941	50591075
ENSE00003565935	50591535	50591639
ENSE00003622897	50621843	50621899
ENSE00003642916	50587831	50588078
ENSE00003642994	50623177	50623248

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 99.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1551 / max 488.0229, expressed in 1184 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139498	5.7422	979
139496	2.2662	638
139497	0.6969	200
139493	0.1690	83
139499	0.1575	76
139495	0.0690	30
139494	0.0543	20

Top tissues by expression

255 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.00	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.91	gold quality
endothelial cell	CL:0000115	98.44	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.20	gold quality
dorsal root ganglion	UBERON:0000044	98.12	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.86	gold quality
substantia nigra pars compacta	UBERON:0001965	97.64	gold quality
pons	UBERON:0000988	97.38	gold quality
superior frontal gyrus	UBERON:0002661	97.10	gold quality
entorhinal cortex	UBERON:0002728	97.06	gold quality
superior vestibular nucleus	UBERON:0007227	97.01	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.94	gold quality
prefrontal cortex	UBERON:0000451	96.81	gold quality
occipital lobe	UBERON:0002021	96.59	gold quality
primary visual cortex	UBERON:0002436	96.50	gold quality
parietal lobe	UBERON:0001872	96.49	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.47	gold quality
medulla oblongata	UBERON:0001896	96.34	gold quality
postcentral gyrus	UBERON:0002581	96.25	gold quality
frontal cortex	UBERON:0001870	96.22	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.13	gold quality
trigeminal ganglion	UBERON:0001675	95.94	gold quality
dorsal plus ventral thalamus	UBERON:0001897	95.91	gold quality
lateral globus pallidus	UBERON:0002476	95.73	gold quality
neocortex	UBERON:0001950	95.58	gold quality
cortical plate	UBERON:0005343	95.52	gold quality
cerebral cortex	UBERON:0000956	95.50	gold quality
ventral tegmental area	UBERON:0002691	95.00	gold quality
right frontal lobe	UBERON:0002810	94.46	gold quality
inferior vagus X ganglion	UBERON:0005363	94.34	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	3415.22
E-MTAB-6701	yes	2845.32
E-CURD-79	yes	2714.20
E-MTAB-10485	yes	2182.42
E-MTAB-9154	yes	1802.33
E-MTAB-8142	yes	110.68
E-HCAD-1	yes	41.82
E-HCAD-9	yes	18.38
E-CURD-46	yes	18.35
E-GEOD-137537	yes	8.81
E-HCAD-10	yes	7.38
E-ANND-3	yes	4.95
E-CURD-135	no	3248.45
E-GEOD-134144	no	2915.48
E-MTAB-6108	no	1369.19

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

82 targeting ATL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-153-5P	99.89	73.86	6317

Literature-anchored findings (GeneRIF, showing 40)

• This study reports a novel mutation in the SPG3A gene in a family with spastic paraplegia, further confirming that mutations in this gene cause autosomal dominant hereditary spastic paraplegia. (PMID:12112092)
• identification as a multimeric integral membrane GTPase that may be involved in Golgi membrane dynamics or vesicle trafficking (PMID:14506257)
• The R239C mutation was found to co-segregate with autosomal dominant hereditary spastic paraplegia (ADHSP) in one English ADHSP family confirming a widespread prevalence for this commonly occurring mutation (PMID:14607301)
• In a family with autosomal dominant spastic paraplegia, heterozygous substitution in exon 12 exchanges arginine for tryptophan at position 415 (R415W) abolishing an MSP I recognition site (CC’GG). (PMID:15184642)
• This paper report a novel mutation in the SPG3A gene in an African American family with an infantile onset of autosomal dominant hereditary spastic paraplegia. (PMID:15477516)
• Three novel mutations were found in exons 4, 9, and 12 of the atlastin gene and the common R239C mutation located in exon 7 was confirmed in a 7th family of European origin (PMID:15517445)
• All mutations of atlastin1 in young-onset autosomal dominant spastic paraplegia patients in France were found in exons 7, 8, 12, and 13. These exons should be given priority when performing molecular diagnoses for SPG3A. (PMID:15596607)
• This study report a new atlastin(R495W) mutation causing spastic paraplegia in association with axonal neuropathy in an Italian family. (PMID:15742100)
• Spastin and atlastin, two proteins mutated in autosomal-dominant hereditary spastic paraplegia, are binding partners. (PMID:16339213)
• Seven families with six different SPG3A mutations were identified among 106 with autosomal dominant hereditary spastic paraplegia (HSP). (PMID:16401858)
• This study identified a novel SPG3A mutation (L157W) in the proband and her affected child. (PMID:16533974)
• Interaction between atlastin and spastin may define a cellular biological pathway that is important in axon maintenance, the failure of which may be pathogenetically relevant. (PMID:16815977)
• Atlastin plays a role in vesicle trafficking in the ER/Golgi interface (PMID:17321752)
• This study identified Y469C mutation in SPG3A in Japanese family with hereditary spastic paraplegia. (PMID:17380240)
• In a large SPG3A screen of 70 hereditary spastic paraplegia subjects, a novel in-frame deletion, p.del436N, was identified which affects neither the guanosine triphosphatase activity of atlastin nor interactions between atlastin and spastin. (PMID:17427918)
• Mutations in SPG3A represent an important cause of patients in the overall hereditary spastic paraplegia population. (PMID:17502470)
• identification of one novel and one known SPG3A mutation in screening 20 families and 23 sporadic cases of hereditary spastic paraplegia in Chinese Han population (PMID:17531128)
• We describe a severe case of herediatry spastic paraplegia, extending the clinical spectrum of SPG3A mutations to a very severe and very early complicated phenotype. (PMID:18446315)
• in dominant spastic paraplegia families, mutation analysis was performed for SPG4 & SPG3A genes; identified 10 novel mutations: one in SPG3A & 9 in SPG4 genes; most of the novel mutations were frameshift or nonsense (80%) (PMID:18664244)
• In hereditary spastic paraplegia, one new disease causing sequence variant and one non pathogenic non synonymous variant were found in SPG3A. (PMID:19423133)
• Four novel SPG3A/atlastin mutations identified in autosomal dominant hereditary spastic paraplegia kindreds with intra-familial variability in age of onset and complex phenotype (PMID:19459885)
• Atlastin-1 might be implicated in membrane tubulation and vesiculation and may participate in the formation as well as the function of the endoplasmic reticulum. (PMID:19573020)
• Using DNA mutation analysis, the authors identified an SPG3A missense mutation (p.R239C) in a Chinese family where three members have early-onset pure spastic paraplegia. (PMID:19652243)
• study describes two patients with Silver phenotype including one with a novel SPG4 (Spastin) mutation and a second with a known SPG 4 mutation (previously unassociated with this phenotype) and a concomitant previously unreported mutation in SPG3A (PMID:19730024)
• Data report a new heterozygous S398F mutation in exon 12 of the SPG3A gene causing a very early-onset spastic paraplegia in association with motor axonal neuropathy resembling diplegic cerebral palsy. (PMID:19735987)
• a new mutation in SPG3A in Italian family manifesting a complex phenotype characterized by cerebellar involvement and amyotrophic lateral sclerosis-like syndrome (PMID:19768483)
• Hereditary spastic paraplegias (HSP) proteins atlastin-1, spastin, and REEP1 interact within the tubularER membrane in corticospinal neurons to coordinate ER shaping and microtubule dynamics. (PMID:20200447)
• previously unreported autosomal dominant mutations in the atlastin gene in hereditary spastic paraplegia (PMID:20718791)
• In a large cohort of Spanish patients with spastic paraplegia, SPAST and ATL1 mutations were found in 15% of the cases (PMID:20932283)
• This study highlights an unexpected major role for atlastin-1 in the function of sensory neurons and identifies hereditary sensory neuropathy type I and Spastic paraplegia 3, autosomal dominant as allelic disorders. (PMID:21194679)
• a model for nucleotide-dependent regulation of atlastin with implications for membrane fusion. This mechanism is affected in several mutants associated with HSP, providing insights into disease pathogenesis. (PMID:21220294)
• We identified a novel mutation, c.1040T>C (p. M347T), in a family with axonal neuropathy in addition to spastic paraplegia. (PMID:21321493)
• experiments also show that membrane fusion is facilitated by the C-terminal cytosolic tails following the two transmembrane segments. Finally, our results show that mutations in ATL1 causing hereditary spastic paraplegia compromise homotypic ER fusion (PMID:21368113)
• increasing the distance of atlastin complex formation from the membrane inhibits fusion, suggesting that this distance is crucial for atlastin to promote fusion (PMID:21930898)
• The N355K atlastin 1 mutation is associated with hereditary sensory neuropathy. (PMID:22340599)
• these results further supports the role of the atlastin-1 of BMP signaling cascade in axonal maintenance and axonal degeneration, which is seen in various types of hereditary spastic paraplegia. (PMID:23079343)
• Three novel ATL1 mutations are identified in a cohort of patients with upper motor neuron syndrome. (PMID:23108492)
• frontal glucose hypometabolism was associated with frontal cognitive impairment indicating that widespread neuropathology associated with mutations in the SPG3A gene (PMID:23233086)
• The cytoplasmic domain of atlastin acts as a tether and homotypic interactions are timed by GTP binding and hydrolysis. (PMID:23334294)
• The atlastin-mediated fusion of ER membranes is important for LD size regulation. (PMID:23684613)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	atl1	ENSDARG00000060481
mus_musculus	Atl1	ENSMUSG00000021066
rattus_norvegicus	Atl1	ENSRNOG00000005063
drosophila_melanogaster	atl	FBGN0039213

Paralogs (10): GBP3 (ENSG00000117226), GBP1 (ENSG00000117228), ATL2 (ENSG00000119787), RNF112 (ENSG00000128482), GBP5 (ENSG00000154451), GBP2 (ENSG00000162645), GBP4 (ENSG00000162654), GBP6 (ENSG00000183347), ATL3 (ENSG00000184743), GBP7 (ENSG00000213512)

Protein

Protein identifiers

Atlastin-1 — Q8WXF7 (reviewed: Q8WXF7)

Alternative names: Brain-specific GTP-binding protein, GTP-binding protein 3, Guanine nucleotide-binding protein 3, Spastic paraplegia 3 protein A

All UniProt accessions (13): A0A0S2Z5A2, A0A0S2Z5B0, A0A6I8PIS8, A0A6I8PUC8, A0A804HLC1, A0AAQ5BH54, Q8WXF7, G3V321, G3V334, G3V4Y8, G3V5T4, H0YJ65, H0YJA7

UniProt curated annotations — full annotation on UniProt →

Function. Atlastin-1 (ATL1) is a membrane-anchored GTPase that mediates the GTP-dependent fusion of endoplasmic reticulum (ER) membranes, maintaining the continuous ER network. It facilitates the formation of three-way junctions where ER tubules intersect. Two atlastin-1 on neighboring ER tubules bind GTP and form loose homodimers through the GB1/RHD3-type G domains and 3HB regions. Upon GTP hydrolysis, the 3HB regions tighten, pulling the membranes together to drive their fusion. After fusion, the homodimer disassembles upon release of inorganic phosphate (Pi). Subsequently, GDP dissociates, resetting the monomers to a conformation ready for a new fusion cycle. May also regulate more or less directly Golgi biogenesis. Indirectly regulates axonal development.

Subunit / interactions. Monomeric and homodimeric. The homodimer, transiently formed by two molecules on opposing membranes, is the active form mediating ER membrane fusion. Interacts with REEP1, REEP5, RTN3 and RTN4 (via the transmembrane region); these proteins are involved in endoplasmic reticulum tubular network organization. Interacts with ZFYVE27; both proteins are involved in endoplasmic reticulum tubular network organization. Interacts with ARL6IP1; both proteins are involved in endoplasmic reticulum tubular network organization. Interacts with SPAST; the interaction is direct, could recruit SPAST to Golgi membranes. Interacts (via N-terminal region) with MAP4K4 (via CNH regulatory domain). May interact with TMED2. Interacts with CPT1C.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus membrane. Cell projection. Axon.

Tissue specificity. Expressed predominantly in the adult and fetal central nervous system. Measurable expression in all tissues examined, although expression in adult brain is at least 50-fold higher than in other tissues. Detected predominantly in pyramidal neurons in the cerebral cortex and the hippocampus of the brain. Expressed in upper and lower motor neurons (at protein level).

Post-translational modifications. Phosphorylated. Phosphorylation, by different kinases, of the N-terminal hypervariable region (HVR) regulates the ATL1-mediated membrane tethering step.

Disease relevance. Spastic paraplegia 3, autosomal dominant (SPG3) [MIM:182600] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. The disease is caused by variants affecting the gene represented in this entry. Neuropathy, hereditary sensory, 1D (HSN1D) [MIM:613708] A disease characterized by adult-onset distal axonal sensory neuropathy leading to mutilating ulcerations as well as hyporeflexia. Some patients may show features suggesting upper neuron involvement. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The N-terminal hypervariable region (HVR) regulates ATL1-mediated membrane tethering by organizing ATL1 into a lattice structure on the same membrane. It does not affect GTP hydrolysis or membrane fusion. It has no effect on the GTP hydrolysis and fusion steps. The GB1/RHD3-type G domain mediates GTP-binding and hydrolysis as well as homodimerization. The two three-helix bundle (3HB) regions in the homodimer are loosely associated initially, but they tighten upon GTP hydrolysis, facilitating the fusion of membranes. The C-terminal autoinhibitory domain negatively regulates the GTPase-dependent fusogenic activity without affecting GTP-binding.

Similarity. Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WXF7-1	1	yes
Q8WXF7-2	2

RefSeq proteins (3): NP_001121185, NP_056999, NP_853629 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015894	Guanylate-bd_N	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030386	G_GB1_RHD3_dom	Domain
IPR036543	Guanylate-bd_C_sf	Homologous_superfamily

Pfam: PF02263

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (116 total): sequence variant 23, binding site 21, strand 17, mutagenesis site 16, helix 14, turn 7, region of interest 5, modified residue 4, topological domain 3, transmembrane region 2, chain 1, coiled-coil region 1, splice variant 1, domain 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
6B9F	X-RAY DIFFRACTION	1.9
7OL3	X-RAY DIFFRACTION	1.9
6B9D	X-RAY DIFFRACTION	1.95
6B9E	X-RAY DIFFRACTION	1.99
4IDO	X-RAY DIFFRACTION	2.09
6XJN	X-RAY DIFFRACTION	2.2
4IDN	X-RAY DIFFRACTION	2.25
4IDQ	X-RAY DIFFRACTION	2.29
4IDP	X-RAY DIFFRACTION	2.59
3Q5D	X-RAY DIFFRACTION	2.7
3QNU	X-RAY DIFFRACTION	2.8
3QOF	X-RAY DIFFRACTION	2.8
6B9G	X-RAY DIFFRACTION	3
3Q5E	X-RAY DIFFRACTION	3.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXF7-F1	86.49	0.65

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (21): 77; 77; 78; 78; 79; 79; 80; 80; 81; 81; 81; 82 …

Post-translational modifications (4): 10, 22, 23, 395

Mutagenesis-validated functional residues (16):

Position	Phenotype
10	no effect on gtpase-dependent fusogenic activity. no effect on the membrane tethering step.
10	decreased gtpase-dependent fusogenic activity. specifically alters the membrane tethering step.
22	no effect on gtpase-dependent fusogenic activity; when associated with a-23.
22	no effect on gtpase-dependent fusogenic activity. no effect on the membrane tethering step; when associated with e-23.
23	no effect on gtpase-dependent fusogenic activity; when associated with a-22.
23	no effect on gtpase-dependent fusogenic activity. no effect on the membrane tethering step; when associated with e-22.
77	abolishes gtpase activity and impairs homodimerization.
77	abolishes homodimerization. loss of gtpase-dependent fusogenic activity.
80	changed endoplasmic reticulum tubular network organization. alters endoplasmic reticulum morphogenesis.
151	changed endoplasmic reticulum tubular network organization. endoplasmic reticulum and golgi morphology are affected.
162	changed endoplasmic reticulum tubular network organization. endoplasmic reticulum and golgi morphology are affected.
191	abolishes homodimerization.
247	impairs homodimerization and gtpase activity.
398	changed endoplasmic reticulum tubular network organization. alters homodimerization. endoplasmic reticulum and golgi mor
443	changed endoplasmic reticulum tubular network membrane organization.
507	loss of gtpase-dependent fusogenic activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 283 (showing top): RNGTGGGC_UNKNOWN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_MEMBRANE_FUSION, GOBP_NEUROGENESIS, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_ORGANELLE_MEMBRANE_FUSION, ZIC1_01, TGANTCA_AP1_C, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOCC_NEURON_PROJECTION, RFX1_02, GOBP_MEMBRANE_ORGANIZATION, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_ENDOPLASMIC_RETICULUM_ORGANIZATION

GO Biological Process (5): endoplasmic reticulum organization (GO:0007029), axonogenesis (GO:0007409), endoplasmic reticulum membrane fusion (GO:0016320), protein homooligomerization (GO:0051260), endoplasmic reticulum tubular network membrane organization (GO:1990809)

GO Molecular Function (7): GTPase activity (GO:0003924), GTP binding (GO:0005525), identical protein binding (GO:0042802), GTPase-dependent fusogenic activity (GO:0140523), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (12): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), axon (GO:0030424), endoplasmic reticulum tubular network (GO:0071782), endoplasmic reticulum tubular network membrane (GO:0098826), Golgi cis cisterna membrane (GO:1990674), cytoplasm (GO:0005737), membrane (GO:0016020), cell projection (GO:0042995), endoplasmic reticulum subcompartment (GO:0098827)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
endoplasmic reticulum membrane organization	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
endoplasmic reticulum subcompartment	2
organelle organization	1
endomembrane system organization	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
endoplasmic reticulum organization	1
organelle membrane fusion	1
protein complex oligomerization	1
endoplasmic reticulum tubular network organization	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
GTPase activity	1
membrane fusion	1
fusogenic activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
neuron projection	1
endoplasmic reticulum membrane	1
endoplasmic reticulum tubular network	1
Golgi cis cisterna	1
Golgi cisterna membrane	1
intracellular anatomical structure	1
endoplasmic reticulum	1
organelle subcompartment	1

Protein interactions and networks

STRING

992 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATL1	SPAST	Q9UBP0	995
ATL1	REEP1	Q9H902	982
ATL1	NIPA1	Q7RTP0	861
ATL1	SPART	Q8N0X7	841
ATL1	RTN2	O75298	838
ATL1	RTN1	Q16799	822
ATL1	REEP5	Q00765	817
ATL1	ARL6IP1	Q15041	752
ATL1	SSNA1	O43805	749
ATL1	ZFYVE27	Q5T4F4	744
ATL1	REEP2	Q9BRK0	735
ATL1	SPG11	Q96JI7	734
ATL1	WASHC5	Q12768	728
ATL1	ZFYVE26	Q68DK2	703
ATL1	CHMP1B	Q7LBR1	698

IntAct

129 interactions, top by confidence:

A	B	Type	Score
ATL1	ATL1	psi-mi:“MI:0407”(direct interaction)	0.850
ATL1	DNM2	psi-mi:“MI:0915”(physical association)	0.560
ATL1		psi-mi:“MI:0915”(physical association)	0.560
LMNA	ATL1	psi-mi:“MI:0915”(physical association)	0.560
ATL1	NDUFV2	psi-mi:“MI:0915”(physical association)	0.560
ATL1	NF2	psi-mi:“MI:0915”(physical association)	0.560
ATL1	PEX7	psi-mi:“MI:0915”(physical association)	0.560
ATL1	PPT1	psi-mi:“MI:0915”(physical association)	0.560
ATL1	PRNP	psi-mi:“MI:0915”(physical association)	0.560
ATL1	PRPH	psi-mi:“MI:0915”(physical association)	0.560
ATL1	SMN1	psi-mi:“MI:0915”(physical association)	0.560
TSC1	ATL1	psi-mi:“MI:0915”(physical association)	0.560
ATL1	RAB7A	psi-mi:“MI:0915”(physical association)	0.560
ATL1	YARS1	psi-mi:“MI:0915”(physical association)	0.560
ATL1	OPTN	psi-mi:“MI:0915”(physical association)	0.560
ATL1	JPH3	psi-mi:“MI:0915”(physical association)	0.560
ATL1	PANK2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (85): ATL1 (Affinity Capture-MS), ATL1 (Affinity Capture-MS), ATL1 (Proximity Label-MS), ATL1 (Proximity Label-MS), ATL1 (Proximity Label-MS), ATL1 (Proximity Label-MS), ATL1 (Affinity Capture-MS), ATL1 (Proximity Label-MS), ATL1 (Proximity Label-MS), ATL1 (Proximity Label-MS), ATL1 (Proximity Label-MS), ATL1 (Proximity Label-MS), ATL1 (Proximity Label-MS), ATL1 (Proximity Label-MS), ATL1 (Proximity Label-MS)

ESM2 similar proteins: A5PKI3, A7E2Z9, A8MWY0, B0BLS9, D4A1F2, F1MF74, O94851, P58335, P58499, P97259, P97675, P97805, Q04499, Q08834, Q09328, Q0ZHH6, Q2M146, Q3UZV7, Q58D72, Q5EBA1, Q5I598, Q5R4P1, Q60HD2, Q6DD88, Q6DDW2, Q6DFX2, Q6DYE8, Q6GQC1, Q6NVG7, Q6PA06, Q6PST4, Q7ZYY4, Q80YD1, Q810F4, Q8BH66, Q8BML1, Q8IYB8, Q8K1B9, Q8NHH9, Q8R4G6

Diamond homologs: A0JN74, A6NK02, B1H278, I1YAP6, O00635, O19085, O70418, O77666, P0C8K8, P19474, P62603, Q08DF2, Q0PF16, Q0ZHH6, Q12899, Q14258, Q1ACD5, Q1ACD6, Q1ACD7, Q1ACD8, Q1XHT8, Q1XHU0, Q2T9Z0, Q2YEM8, Q2YEM9, Q2YEN0, Q2YEN2, Q3UWA4, Q3UWZ0, Q3ZEE5, Q495X7, Q587N6, Q587N7, Q58D72, Q5BK82, Q5BN31, Q5C8T6, Q5C8T8, Q5C8U1, Q5C8U3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
COPI-mediated anterograde transport	6	18.8×	3e-05
COPI-dependent Golgi-to-ER retrograde traffic	5	15.8×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	5	37.5×	1e-04
endoplasmic reticulum to Golgi vesicle-mediated transport	6	18.1×	2e-04
Golgi organization	5	14.9×	1e-03
endocytosis	5	10.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

698 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	40
Likely pathogenic	41
Uncertain significance	306
Likely benign	171
Benign	46

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072586	NM_015915.5(ATL1):c.565C>G (p.His189Asp)	Pathogenic
1275819	NM_015915.5(ATL1):c.1501C>T (p.Arg501Ter)	Pathogenic
1456145	NM_015915.5(ATL1):c.773A>T (p.His258Leu)	Pathogenic
157549	NM_015915.5(ATL1):c.353G>A (p.Arg118Gln)	Pathogenic
191046	NM_015915.5(ATL1):c.988A>T (p.Lys330Ter)	Pathogenic
1996944	NM_015915.5(ATL1):c.584A>C (p.Glu195Ala)	Pathogenic
2037429	NM_015915.5(ATL1):c.1101C>A (p.Tyr367Ter)	Pathogenic
208489	NM_015915.5(ATL1):c.596T>A (p.Leu199Gln)	Pathogenic
21531	NM_015915.5(ATL1):c.467C>T (p.Thr156Ile)	Pathogenic
2571508	NM_015915.5(ATL1):c.1024C>T (p.Pro342Ser)	Pathogenic
2571511	NM_015915.5(ATL1):c.1193C>T (p.Ser398Phe)	Pathogenic
2571515	NM_015915.5(ATL1):c.1319A>C (p.Asn440Thr)	Pathogenic
2826561	NM_015915.5(ATL1):c.1030_1040del (p.Pro344fs)	Pathogenic
2860253	NM_015915.5(ATL1):c.336G>A (p.Trp112Ter)	Pathogenic
30579	NM_015915.5(ATL1):c.1065C>A (p.Asn355Lys)	Pathogenic
3244009	NC_000014.8:g.(?51087297)(51095200_?)del	Pathogenic
3606208	NM_015915.5(ATL1):c.56_57del (p.Thr18_Tyr19insTer)	Pathogenic
3639402	NM_015915.5(ATL1):c.521del (p.Gln174fs)	Pathogenic
3729603	NM_015915.5(ATL1):c.1008T>G (p.Tyr336Ter)	Pathogenic
4081053	NM_015915.5(ATL1):c.523-2A>C	Pathogenic
4347	NM_015915.5(ATL1):c.776C>A (p.Ser259Tyr)	Pathogenic
4348	NM_015915.5(ATL1):c.773A>G (p.His258Arg)	Pathogenic
4351	NM_015915.5(ATL1):c.1222A>G (p.Met408Val)	Pathogenic
4353	NM_015915.5(ATL1):c.470T>G (p.Leu157Trp)	Pathogenic
576063	NM_015915.5(ATL1):c.572A>G (p.Gln191Arg)	Pathogenic
640860	NM_015915.5(ATL1):c.1488C>A (p.Tyr496Ter)	Pathogenic
654142	NM_015915.5(ATL1):c.1048G>A (p.Ala350Thr)	Pathogenic
803025	NM_015915.5(ATL1):c.488T>C (p.Val163Ala)	Pathogenic
803026	NM_015915.5(ATL1):c.1223T>C (p.Met408Thr)	Pathogenic
831440	NC_000014.9:g.(?50560256)(50632349_?)del	Pathogenic

SpliceAI

1711 predictions. Top by Δscore:

Variant	Effect	Δscore
14:50560295:TTGGG:T	donor_gain	1.0000
14:50560296:TGGG:T	donor_gain	1.0000
14:50560297:GGG:G	donor_gain	1.0000
14:50560297:GGGG:G	donor_gain	1.0000
14:50560298:GG:G	donor_gain	1.0000
14:50560298:GGG:G	donor_gain	1.0000
14:50560299:GG:G	donor_gain	1.0000
14:50560299:GGTG:G	donor_loss	1.0000
14:50560300:G:GG	donor_gain	1.0000
14:50560300:GTG:G	donor_loss	1.0000
14:50560301:T:A	donor_loss	1.0000
14:50587992:G:GT	donor_gain	1.0000
14:50588076:CAGG:C	donor_loss	1.0000
14:50588077:AGGTA:A	donor_loss	1.0000
14:50588078:GG:G	donor_loss	1.0000
14:50588079:G:T	donor_loss	1.0000
14:50588087:G:GT	donor_gain	1.0000
14:50590935:TTATA:T	acceptor_loss	1.0000
14:50590936:TATA:T	acceptor_loss	1.0000
14:50590938:TAG:T	acceptor_loss	1.0000
14:50590939:A:AG	acceptor_gain	1.0000
14:50590940:G:GG	acceptor_gain	1.0000
14:50591073:AAGGT:A	donor_loss	1.0000
14:50591074:AG:A	donor_loss	1.0000
14:50591075:GG:G	donor_loss	1.0000
14:50591076:GTATG:G	donor_loss	1.0000
14:50591531:GTA:G	acceptor_loss	1.0000
14:50591533:A:AG	acceptor_gain	1.0000
14:50591533:A:T	acceptor_loss	1.0000
14:50591534:G:GG	acceptor_gain	1.0000

AlphaMissense

3681 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:50588011:T:A	V72D	1.000
14:50588014:C:A	A73D	1.000
14:50588016:G:A	G74R	1.000
14:50588016:G:C	G74R	1.000
14:50588017:G:A	G74E	1.000
14:50588017:G:T	G74V	1.000
14:50588022:T:C	F76L	1.000
14:50588024:T:A	F76L	1.000
14:50588024:T:G	F76L	1.000
14:50588025:A:G	R77G	1.000
14:50588026:G:C	R77T	1.000
14:50588026:G:T	R77I	1.000
14:50588027:A:C	R77S	1.000
14:50588027:A:T	R77S	1.000
14:50588031:G:A	G79R	1.000
14:50588031:G:C	G79R	1.000
14:50588032:G:A	G79E	1.000
14:50588032:G:C	G79A	1.000
14:50588032:G:T	G79V	1.000
14:50588034:A:C	K80Q	1.000
14:50588035:A:T	K80I	1.000
14:50588036:A:C	K80N	1.000
14:50588036:A:T	K80N	1.000
14:50588037:T:C	S81P	1.000
14:50588038:C:T	S81L	1.000
14:50588040:T:C	F82L	1.000
14:50588042:C:A	F82L	1.000
14:50588042:C:G	F82L	1.000
14:50590986:T:C	F110L	1.000
14:50590987:T:C	F110S	1.000

dbSNP variants (sampled 300 via entrez): RS1000025602 (14:50541257 AT>A), RS1000056984 (14:50602537 T>G), RS1000059913 (14:50623761 T>C), RS1000093605 (14:50587090 C>A), RS1000106152 (14:50616776 A>C,G), RS1000106994 (14:50567741 C>A,G), RS1000132948 (14:50623963 G>A), RS1000157670 (14:50594372 T>C), RS1000194563 (14:50563351 G>A,T), RS1000212015 (14:50602347 C>T), RS1000213935 (14:50598492 C>G), RS1000271235 (14:50579980 TA>T), RS1000292067 (14:50548729 C>T), RS1000302415 (14:50617058 T>C), RS1000321005 (14:50559887 T>G)

Disease associations

OMIM: gene MIM:606439 | disease phenotypes: MIM:182600, MIM:613708, MIM:303350, MIM:118220, MIM:616559

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary spastic paraplegia 3A	Definitive	Semidominant
neuropathy, hereditary sensory, type 1D	Definitive	Autosomal dominant
hereditary sensory and autonomic neuropathy type 1	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
neuropathy, hereditary sensory, type 1D	Definitive	AD

Mondo (7): hereditary spastic paraplegia 3A (MONDO:0008437), neuropathy, hereditary sensory, type 1D (MONDO:0013381), congenital nervous system disorder (MONDO:0002320), hereditary spastic paraplegia (MONDO:0019064), Charcot-Marie-Tooth disease (MONDO:0015626), Noonan syndrome 9 (MONDO:0014691), hereditary sensory and autonomic neuropathy type 1 (MONDO:0018213)

Orphanet (5): Autosomal dominant spastic paraplegia type 3 (Orphanet:100984), Hereditary sensory and autonomic neuropathy type 1 (Orphanet:36386), Hereditary spastic paraplegia (Orphanet:685), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Noonan syndrome (Orphanet:648)

HPO phenotypes

73 total (30 of 73 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000365	Hearing impairment
HP:0000962	Hyperkeratosis
HP:0001026	Penetrating foot ulcers
HP:0001058	Poor wound healing
HP:0001256	Mild intellectual disability
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001270	Motor delay
HP:0001288	Gait disturbance
HP:0001324	Muscle weakness
HP:0001347	Hyperreflexia
HP:0001510	Growth delay
HP:0001761	Pes cavus
HP:0002020	Gastroesophageal reflux
HP:0002061	Lower limb spasticity
HP:0002063	Rigidity
HP:0002064	Spastic gait
HP:0002067	Bradykinesia
HP:0002079	Hypoplasia of the corpus callosum
HP:0002141	Gait imbalance
HP:0002166	Impaired vibration sensation in the lower limbs
HP:0002270	Abnormality of the autonomic nervous system
HP:0002314	Degeneration of the lateral corticospinal tracts
HP:0002359	Frequent falls
HP:0002395	Lower limb hyperreflexia
HP:0002460	Distal muscle weakness
HP:0002495	Impaired vibratory sensation

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000579_60	Cognitive performance	3.000000e-07
GCST002312_10	Periodontal disease-related phenotype (Socransky)	8.000000e-06
GCST002479_13	Lupus nephritis in systemic lupus erythematosus	3.000000e-07
GCST004858_18	Dupuytren’s disease	2.000000e-17
GCST007294_112	Body fat distribution (trunk fat ratio)	3.000000e-08
GCST007294_152	Body fat distribution (trunk fat ratio)	1.000000e-12
GCST007294_92	Body fat distribution (trunk fat ratio)	8.000000e-06
GCST007295_114	Body fat distribution (leg fat ratio)	3.000000e-08
GCST007295_16	Body fat distribution (leg fat ratio)	1.000000e-11
GCST007295_96	Body fat distribution (leg fat ratio)	2.000000e-18
GCST012490_218	Femur bone mineral density x serum urate levels interaction	2.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0004229	Dupuytren Contracture
EFO:0004341	body fat distribution
EFO:0004531	urate measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
C536864	Spastic paraplegia 3, autosomal dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Valproic Acid	decreases expression, increases expression	3
Aflatoxin B1	affects expression, decreases methylation, increases methylation	3
sodium arsenite	increases expression	2
potassium chromate(VI)	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
FR900359	increases phosphorylation	1
tungsten carbide	affects cotreatment, increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
lead acetate	increases expression	1
beta-lapachone	decreases expression	1
propionic acid	decreases expression	1
nickel sulfate	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Cobalt	affects cotreatment, increases expression	1
Cytarabine	increases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_RM26	iSPG3A-6	Induced pluripotent stem cell	Female
CVCL_RM27	iSPG3A-8	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

110 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT04762758	PHASE3	UNKNOWN	Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients
NCT06113055	PHASE2	UNKNOWN	Hereditary Sensory Neuropathy Serine Trial
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT00271635	PHASE2	COMPLETED	Ascorbic Acid Treatment in CMT1A Trial (AATIC)
NCT01401257	PHASE2	COMPLETED	Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A
NCT02561702	PHASE2	COMPLETED	Mexiletine for Muscle Cramps in Charcot Marie Tooth Disease
NCT02967679	PHASE2	COMPLETED	SERENDEM : MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study
NCT03124459	PHASE2	TERMINATED	Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease
NCT03254199	PHASE2	TERMINATED	A Study to Assess the Safety and Effectiveness of FLX-787 in Subjects With Charcot-Marie-Tooth Disease Experiencing Muscle Cramps.
NCT03943290	PHASE2	TERMINATED	Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) and Charcot-Marie Tooth (CMT) Disease Types 1 and X (CMT1 and CMTX)
NCT05777226	PHASE2	UNKNOWN	Research of SORD-CMT Natural History and Epalrestat Treatment
NCT06482437	PHASE2	COMPLETED	Safety and Efficacy of NMD670 in Adult Patients With Type 1 and Type 2 Charcot-Marie-Tooth Disease
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT04180098	Not specified	COMPLETED	Improving Gait Adaptability in Hereditary Spastic Paraplegia
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT01733407	PHASE1/PHASE2	COMPLETED	L-Serine Supplementation in Hereditary Sensory Neuropathy Type 1
NCT02604186	PHASE2/PHASE3	COMPLETED	Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT06948019	PHASE1/PHASE2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT06478238	EARLY_PHASE1	RECRUITING	Calcium Folinate Treatment of Spastic Paraplegia 56
NCT00023075	Not specified	COMPLETED	Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00677768	Not specified	COMPLETED	Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
NCT01568658	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Physical Study of Childhood Nerve and Muscle Disorders
NCT02327845	Not specified	ENROLLING_BY_INVITATION	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT02859428	Not specified	TERMINATED	Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
NCT03104088	Not specified	COMPLETED	Studying Cognition in SPG4
NCT03206190	Not specified	RECRUITING	The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4
NCT03627416	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
NCT03981276	Not specified	RECRUITING	Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
NCT04006418	Not specified	RECRUITING	A Registered Cohort Study on Spastic Paraplegia
NCT04256681	Not specified	COMPLETED	SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP)
NCT04875416	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype and Biomarkers 2
NCT04912609	Not specified	COMPLETED	Trehalose Administration in Subjects With Spastic Paraplegia 11 (3AL-SPG11)
NCT05354622	Not specified	RECRUITING	Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)
NCT05373082	Not specified	COMPLETED	Identification of Modifying Factors in Hereditary Spastic Paraplegia